On Day 3 of ARVO 2025 in Salt Lake City, a dynamic minisymposium peeled back the retinal layers as leading scientists showcased how adaptive optics (AO) imaging is fast transitioning from the research bench to the clinical frontlines.
Featuring five vision science heavyweights including Dr. Jacque Duncan, Dr. Ethan Rossi, Dr. Yuhua Zhang, Dr. Elena Gofas and Dr. Ravi Jonnal, the session laid out the current capabilities of AO to visualize cellular detail in living eyes—and its fast-track trajectory toward influencing diagnostics, trials and treatments.
Adaptive optics: Not just a fad
“Is adaptive optics scanning laser ophthalmoscopy (AOSLO) simply a fad or does it have a real future in clinical trials?” Dr. Jacque Duncan (United States) posed this question early in the session—and spent the next 15 minutes emphatically answering it.
Dr. Duncan described AOSLO as a powerful window into photoreceptor structure and function. She detailed her team’s work with the Foundation Fighting Blindness and the RUSH2A study, where cone spacing measurements over time are being used as structural biomarkers in Usher syndrome and rod-cone dystrophies.1
READ MORE: Advanced Imaging as an Early Biomarker in Diagnosing Usher Syndrome Type 1
“Patients and regulatory agencies may appreciate that we are able to image cone structure using AOSLO,” Dr. Duncan said, “but what they really want to know is how well those cones can perceive light.”
The kicker? AOSLO is now not only measuring structure, but also function—through techniques like optoretinography (ORG) and AO-based psychophysics. “Those non-reflective, non-waveguiding cones certainly have good function,” she noted, presenting evidence from a patient with foveolitis who could still resolve a tumbling “E” with cones that were invisible by standard reflectance imaging.
Making the invisible visible: Autofluorescence & AMD
Next up, Dr. Ethan Rossi (United States) took the stage to discuss high-resolution autofluorescence imaging in age-related macular degeneration (AMD). Using near-infrared excitation and AO systems refined over the past decade, Rossi’s lab has achieved dazzling images of individual retinal pigment epithelium (RPE) cells and even autofluorescent cones.
READ MORE: Protocol for Classifying and Monitoring AMD Patients
“This has taken over a decade of effort,” he admitted, showing dramatic before-and-after images comparing noise-filled early attempts with the crystal-clear visuals now possible.
One of his most arresting insights? Many autofluorescent cones remain even in degenerating areas of retina in retinitis pigmentosa and AMD. “We really want to understand better what this phenomenon is,” Dr. Rossi said. He suspects these autofluorescent cones might serve as a new biomarker, but notes that they appear in healthy eyes too—and so more work is needed to decode their significance.
Cone-level perception: targeting vision with surgical precision
Dr. Yuhua Zhang (United States) zoomed in even further, describing how AO imaging now enables targeted delivery of light stimuli to individual cones. His team is using this capability to map photoreceptor function in patients with achromatopsia and blue-cone monochromacy.
“We see cones regain waveguiding appearance after gene therapy,” he said, referencing ongoing clinical trials. Moreover, Zhang detailed intensity-based optoretinography studies where cones increased or decreased reflectance after visual stimulation—a signal that, while not yet linked to specific vision thresholds, hints at robust future utility for therapy monitoring.
“This approach lets us track the exact same cones across years, even between research sites,” he added, highlighting a powerful use case for both clinical research and patient follow-up.
Inflammation on the map
Dr. Elena Gofas (France) brought a fresh dimension to the AO discussion: neuroinflammation. Her lab in Paris has used phase-contrast AOSLO to detect immune cell infiltration in patients with multiple sclerosis and Leber’s hereditary optic neuropathy.
“We observed immune-like cells clustering around vasculature, even in eyes without optic neuritis,” Gofas reported. “In one patient, cell density spiked before the onset of clinical symptoms.”
Her take-home message is that AO-based cellular imaging may one day serve as a diagnostic tool for subclinical inflammation or as a prognostic marker. With the retina offering a transparent window into the brain, this approach could ripple far beyond ophthalmology.
READ MORE: Visualizing the Retinal Vasculature
Translating the tech: from AO to OCT and beyond
Dr. Ravi Jonnal (United States) closed the session with a call to integrate AO insights into more widely available modalities. “Even if AO systems never reach the clinic at scale,” he said, “they are already transforming how we interpret clinical OCT.”
Jonnal walked the audience through how AO OCT helped correctly identify the origins of hyperreflective bands in traditional OCT images. This detailed anatomical grounding is now being translated into functional imaging approaches using standard clinical systems. His work on “optoretinography without AO” might one day make cone-level functional testing routine in practice.
READ MORE: Advancing Retinal Therapies: Aligning Clinical Endpoints with Patient Priorities
What’s next?
The panel discussion underscored a unifying theme: AO imaging, once relegated to high-end labs, is now deeply embedded in clinical research. With ongoing multicenter trials using standardized phantoms, calibration protocols and functional endpoints, adaptive optics is on the brink of becoming a mainstream clinical tool.
As Dr. Duncan said in closing, “AOSLO may have started as a research curiosity, but its future is nothing short of fabulous.”
Whether you’re tracking photoreceptor survival in RP, probing new color sensations at the cone level, or mapping inflammation in MS, the retina has never been more readable. And if the ARVO 2025 session was any indication, adaptive optics isn’t just showing us what we couldn’t see before—it’s showing us what comes next.
READ MORE: Stay tuned to our daily ARVO 2025 coverage here and never miss an update!
Editor’s Note: Reporting for this story took place during the annual meeting of The Association for Research in Vision and Ophthalmology (ARVO 2025) being held from 4-8 May in Salt Lake City, Utah, United States.
Reference
- Duncan JL, Cheng P, Maguire MG, et al; Foundation Fighting Blindness Consortium Investigator Group. Static Perimetry in the Rate of Progression in USH2A-related Retinal Degeneration (RUSH2A) Study: Assessment Through 2 Years. Am J Ophthalmol. 2023;250:103-110.
